A case of conservatively managed gastric perforation at a recurrent hiatal hernia site after laparoscopic paraesophageal repair.

INTRODUCTION AND IMPORTANCE: Gastric perforation due to a hiatal hernia is a rare cause of acute abdominal pain that often requires surgical intervention. Conservative management for this condition is an effective option in certain cases, although fewer reports of this exist. Herein, we report a unique case of gastric perforation caused by a recurrent hiatal hernia that was successfully treated with conservative management. CASE PRESENTATION: A 74-year-old man developed a high fever and an elevated inflammatory response on the third day after a laparoscopic paraesophageal hernia repair using a mesh. Computed tomography confirmed the recurrence of the hiatal hernia, with gastric fundal prolapse into the mediastinum and surgical emphysema in the gastric wall. This was followed by a gastric perforation within the mediastinum. The patient was treated using an ileus tube through the perforation site. CLINICAL DISCUSSION: In similar cases, if the clinical symptoms are mild, there are no signs of serious infection, and the perforation remains in the mediastinum and can be appropriately drained, conservative treatment is considered an option. CONCLUSION: Under favorable conditions, conservative management can be an option for gastric perforation in patients with recurrent hiatal hernias, which is a serious potential postoperative complication.

Surgical and nutritional outcomes of laparoscopic proximal gastrectomy versus total gastrectomy: a meta-analysis.

BACKGROUND: Laparoscopic proximal gastrectomy (LPG) is regarded as a less invasive surgery than laparoscopic total gastrectomy (LTG) for early gastric cancer located on the proximal side of the stomach. However, whether LPG is more effective than LTG remains unclear. METHODS: A systematic literature search of studies assessing short-term surgical and nutritional outcomes after LPG and LTG was conducted. A meta-analysis of surgical outcomes (operative time, intraoperative estimated blood loss, postoperative complications, and length of hospital stay) and nutritional outcomes (decrease in body weight, albumin, hemoglobin, total protein, and lymphocyte count) was then performed. All of 11 papers are a retrospective cohort study. RESULTS: Eleven studies reported assessments of the above-mentioned outcomes in 883 patients. There was a trend towards shorter operative time and lower blood loss for LPG compared to LTG though not reaching statistical significance. Other surgical outcomes showed no significant differences. Patients who underwent LTG had a significantly lower body weight (95% confidence interval, 3.01-6.05, [Formula: see text] = 4.53, p < 0.01) and hemoglobin level (95% confidence interval, 1.88-5.87, [Formula: see text] = 3.87, p < 0.01) than patients who underwent LPG at 1 year after surgery. There were no significant differences in other nutritional outcomes. CONCLUSIONS: These results indicate LPG had some advantages in postoperative nutrition. However, no significant differences in short-term surgical outcomes were noted between the two operations. Our analysis suggests that LPG may be more beneficial compared with LTG in terms of perioperative and nutritional outcomes for early-stage gastric cancer.

Feasibility of laparoscopic gastrectomy for patients with poor physical status: a retrospective cohort study based on a nationwide registry database in Japan.

BACKGROUND: Laparoscopic gastrectomy (LG) is an established minimally invasive procedure for gastric cancer. However, it is controversial whether LG is useful for patients with poor physical status classified into higher classes of the American Society of Anesthesiologists physical status (ASA-PS) classification. The aim of this study was to determine the feasibility of LG in patients with ASA-PS class ≥ 3. METHODS: We extracted data for a total of 28,160 patients with an ASA-PS class ≥ 3 who underwent distal or total gastrectomy for gastric cancer between January 2013 and December 2017 from the National Clinical Database Japan society for gastroenterological surgery registry. We developed a propensity score model from baseline demographics and comorbidities and matched patients undergoing LG to those undergoing open gastrectomy (OG) using a 1:1 ratio. Mortality and morbidities (within 30 days and in-hospital) were compared between the 6998 matched patient pairs. RESULTS: In-hospital mortality was significantly lower in patients undergoing LG than in those undergoing OG (2.3% vs. 3.0%, p = 0.01), while the 30-day mortality was similar (1.6% vs. 1.5%). The length of hospital stay was significantly shorter in the LG group (median, 14 days vs. 17 days, p < 0.001). The LG group had a significantly lower incidence of postoperative complications in patients with any grade complication (20.3% vs. 22.5%, p = 0.002) as well as those with ≥ grade 3 complications (8.7% vs. 9.8%, p = 0.03). CONCLUSION: LG was associated with decreased in-hospital mortality and a lower incidence of several postoperative complications when compared to OG among patients with poor physical condition.

IGFBP1 Is a Predictive Factor for Haematogenous Metastasis in Patients With Gastric Cancer.

BACKGROUND/AIM: The clinicopathological significance and prognostic value of insulin-like growth factor binding protein 1 (IGFBP1) in gastric cancer have not been investigated to date. This study aimed to investigate the relationship of IGFBP1 expression with clinicopathological variables and prognosis. MATERIALS AND METHODS: The correlation of IGFBP1 expression with the clinicopathological factors and the correlation of clinicopathogical factors with haematogenous metastasis in 219 gastric cancer patients who underwent surgery was examined. RESULTS: High IGFBP1 expression was significantly associated with a poorer disease-specific survival (p<0.001) and relapse-free survival (p<0.001) in univariable analysis although IGFBP1 was not an independent prognostic factor. High IGFBP1 expression was the only independent risk factor of haematogenous metastasis. CONCLUSION: High IGFBP1 expression was associated with haematogenous metastasis and poor survival. IGFBP1 might become a new prognostic factor and a target of molecular targeted therapy of gastric cancer.

A subset of diffuse-type gastric cancer is susceptible to mTOR inhibitors and checkpoint inhibitors.

BACKGROUND: Mechanistic target of rapamycin (mTOR) pathway is essential for the growth of gastric cancer (GC), but mTOR inhibitor everolimus was not effective for the treatment of GCs. The Cancer Genome Atlas (TCGA) researchers reported that most diffuse-type GCs were genomically stable (GS). Pathological analysis suggested that some diffuse-type GCs developed from intestinal-type GCs. METHODS: We established patient-derived xenograft (PDX) lines from diffuse-type GCs, and searched for drugs that suppressed their growth. Diffuse-type GCs were classified into subtypes by their gene expression profiles. RESULTS: mTOR inhibitor temsirolimus strongly suppressed the growth of PDX-derived diffuse-type GC-initiating cells, which was regulated via Wnt-mTOR axis. These cells were microsatellite unstable (MSI) or chromosomally unstable (CIN), inconsistent with TCGA report. Diffuse-type GCs in TCGA cohort could be classified into two clusters, and GS subtype was major in cluster I while CIN and MSI subtypes were predominant in cluster II where PDX-derived diffuse-type GC cells were included. We estimated that about 9 and 55% of the diffuse-type GCs in cluster II were responders to mTOR inhibitors and checkpoint inhibitors, respectively, by identifying PIK3CA mutations and MSI condition in TCGA cohort. These ratios were far greater than those of diffuse-type GCs in cluster I or intestinal-type GCs. Further analysis suggested that diffuse-type GCs in cluster II developed from intestinal-type GCs while those in cluster I from normal gastric epithelial cells. CONCLUSION: mTOR inhibitors and checkpoint inhibitors might be useful for the treatment of a subset of diffuse-type GCs which may develop from intestinal-type GCs.

Intraoperative Body Fluid Amylase as a Novel Indicator of Postgastrectomy Pancreatic Fistula.

BACKGROUND: Although many methods to prevent the development of postoperative pancreatic fistula (POPF) after gastrectomy have been reported, POPF can only be identified after it has occurred. Various therapeutic measures could be taken if signs of POPF could be detected intraoperatively. METHODS: We conducted a prospective study in which we attempted to predict POPF by measuring the intraoperative amylase concentration in the peripancreatic body fluid. To collect the body fluid, three sponges were placed around the pancreas at lymph node station Nos. 6, 8, and 11 during lymphadenectomy. The amylase concentration was measured in the body fluid squeezed from the sponges. We investigated whether the intraoperative body fluid amylase concentration (IBAC) was associated with POPF formation. RESULTS: In total, 109 patients were enrolled from February 2016 to March 2018, and we analyzed 81 eligible patients. Clavien-Dindo grade ≥ II POPF occurred in eight patients (9%). The IBAC was significantly higher in sponges No. 6 (P = 0.044) and No. 8 (P = 0.007). The incidence of POPF was predicted by using an IBAC cutoff value for No. 6 (1047 IU/L; sensitivity 87.5%; specificity 65.0%; positive likelihood ratio 2.5) and No. 8 (400 IU/L; sensitivity 87.5%; specificity 68.5%; positive likelihood value 2.8), respectively. The IBAC in sponge No. 11 tended to be higher (P = 0.054). CONCLUSIONS: By measuring the IBAC, surgeons might predict POPF easily and noninvasively during surgery. This method is one of the most effective ways to predict POPF intraoperatively.

Asymmetric dimethylation at histone H3 arginine 2 by PRMT6 in gastric cancer progression.

Histone modification plays important molecular roles in development and progression of cancers. Dysregulation of histone H3 arginine (R) methylation is still unknown in primary cancer, including gastric cancer (GC). Although PRMT6 contributes to asymmetric dimethylation at H3R2 (H3R2me2as) in cancer cells, its molecular functions are poorly understood in GC. In this study, we assessed H3R2me2as and PRMT6 expression levels in 133 primary GC tissues by immunohistochemistry. Increased H3R2me2as was found in 68 GC (51.1%) cases and independently related to poor prognosis. PRMT6 was overexpressed in 70 GC (52.6%) and strongly correlated with the global H3R2me2as levels (P < 0.001). By analyzing biological functions of PRMT6 in GC cell lines by lentivirus-based systems, PRMT6 overexpression enhanced global H3R2me2as and invasiveness in vitro, while PRMT6 knockout (PRMT6-KO) suppressed these effects and tumorigenicity in vivo. ChIP and microarray assays demonstrated that PRMT6-KO GC cells decreased the enrichments of H3R2me2as at the promoter regions of PCDH7, SCD and IGFBP5, resulting in upregulation of their gene expression. PRMT6 was recruited to the promoter regions of PCDH7 and SCD in the PRMT6-overexpressed cells. Knockdown of tumor suppressor PCDH7 in the PRMT6-KO GC cells elevated cell migration and invasion. PRMT6 expression inversely correlated with PCDH7 expression in primary GC (P = 0.021). Collectively, our findings strongly indicate that H3R2me2as is a strong prognostic indicator of GC patients, and PRMT6-overexpressing GC cells may acquire invasiveness through direct transcriptional inhibition of PCDH7 by increasing H3R2me2as level. Thus, inhibition of the PRMT6-H3R2me2as pathway could be a promising new therapeutic strategy in GC.

Long-term functional outcomes of Roux-en-Y versus Billroth I reconstructions after laparoscopic distal gastrectomy for gastric cancer: a propensity-score matching analysis.

BACKGROUND: Only a few reports discuss long-term functional outcomes and changes observed in patients over several years following a distal gastrectomy. We investigated long-term functional outcomes and changes after laparoscopic distal gastrectomy based on the analysis of postoperative conditions and endoscopic findings observed in patients. METHODS: The study group comprised 159 patients who underwent Roux-en-Y reconstruction following laparoscopic distal gastrectomy (R-Y group) between December 2008 and November 2012 and 78 patients who underwent Billroth I reconstruction (B-I group) between January 2002 and November 2012. To minimize bias between the two groups, propensity scores were calculated using a logistic regression model. The groups were compared with respect to postoperative conditions and endoscopic findings at 1, 3, and 5 years postoperatively. RESULTS: The B-I group demonstrated more frequent heartburn than the R-Y group at 3 and 5 years postoperatively. No significant differences were found in terms of loss of body weight and food intake. Endoscopic findings showed significantly lesser residual food and remnant gastritis in the R-Y group at each annual postoperative follow-up. The incidence of bile reflux and reflux esophagitis in the B-I group gradually increased over the years and showed a significant difference at the culmination of the 5-year postoperative follow-up, compared to the R-Y group. CONCLUSIONS: Roux-en-Y reconstruction was superior to Billroth I reconstruction in terms of frequency of occurrence of residual food, bile reflux, remnant gastritis, and reflux esophagitis in the long term. Differences between the two methods became more evident as the follow-up period lengthened.

Prognostic Significance of High EphA1-4 Expression Levels in Locally Advanced Gastric Cancer.

BACKGROUND/AIM: Erythropoietin-producing hepatocellular carcinoma receptor A (EphA) is associated with angiogenesis and invasive tumor progression. In this study, we evaluated the EphA1-4 expression levels in advanced gastric cancer. PATIENTS AND METHODS: Tumor tissues obtained from 114 patients with advanced gastric adenocarcinoma who underwent gastrectomy were analyzed. In addition, the impact of EPHA 1-4 mRNA expression on survival was analyzed using the Kaplan-Meier plotter database on the website. RESULTS: High EphA 1, 2, and 4 expression levels were significantly related to recurrence (p<0.01, p=0.04, and p<0.01). Both high EphA 1 and 4 expression levels were independent predictors of relapse-free interval (hazard ratio [HR]=2.0, p=0.03; HR=2.4, p=0.03) and disease-specific survival (HR=2.0, 95% p=0.03; HR=2.5, p=0.02) on multivariate analysis. In the Kaplan-Meier plotter database, high EPHA2 mRNA expression was significantly associated with poor survival in patients with gastric cancer (p=0.0098), and high expression levels of EPHA1 and 4 tended to be associated with poor survival (p=0.050, p=0.052). CONCLUSION: EphA 1, 2, and 4 may play key roles in recurrence and survival in patients with advanced gastric cancer.

Laparoscopic Distal Gastrectomy is Feasible in Very Elderly Patients as Compared with Open Distal Gastrectomy.

Laparoscopic gastrectomy was shown to be feasible even in elderly patients in many retrospective case-controlled studies. However, the definition of elderly differed among those studies, such as an age of 65, 70, or 75 years or older. This study was conducted to elucidate the advantages of laparoscopic distal gastrectomy (LDG) in very elderly (≥80 years) patients, and comprised 70 patients, 45 of whom underwent LDG and 25 underwent open distal gastrectomy (ODG) between 2004 and September 2016. LDG had significantly less estimated blood loss (p < .01), earlier flatus (p < .01), earlier food intake (p < .01), and shorter hospitalization (p < .01) as compared with ODG. No significant difference between LDG and ODG was found in the incidence of postoperative surgical complications (p = .40), although LDG tended to reduce overall and medical postoperative complications (p = .11 and .09, respectively). LDG might be a feasible, beneficial treatment with good short-term outcomes in very elderly patients with gastric cancer.

Feasibility of laparoscopic total gastrectomy in overweight patients: Implications of less impact of overweight on laparoscopic versus open approach.

AIM: To investigate safety and oncological feasibility of laparoscopic total gastrectomy (LTG) in overweight (OW) patients. METHODS: Patients who underwent total gastrectomy (110 laparoscopic, 211 open) for gastric cancer between January 1999 and July 2016 were included. Propensity score matching selected 152 patients (76 laparoscopic, 76 open), which were subsequently divided into the OW (≥ 25) or non-OW (< 25) group by body mass index. Postoperative outcomes of laparoscopic versus open approaches were compared between OW and non-OW groups. RESULTS: In the propensity-matched population, baseline characteristics were comparable between the OW and non-OW groups for the laparoscopy and open groups. In the laparoscopy group, operative time was longer (P = 0.01) in the OW group, however, other perioperative results including complication rates were comparable between the non-OW and OW groups. In the open group, number of retrieved lymph nodes were less (P = 0.03) and local complication rate was more frequent (P = 0.03) in the OW group. CONCLUSION: LTG in OW patients remains technically challenging but can be performed safely. Our findings imply that OW has a lesser effect on the laparoscopic versus open approach to total gastrectomy.

Long- and short-term outcomes of laparoscopic gastrectomy versus open gastrectomy in patients with clinically and pathological locally advanced gastric cancer: a propensity-score matching analysis.

BACKGROUND: Laparoscopic (laparoscopy-assisted) gastrectomy (LG) has several short-term benefits as compared with open distal gastrectomy (OG) in patients with advanced gastric cancer (AGC). Survival rates did not differ significantly between LG and OG in retrospective studies of AGC, although some studies included unmatched groups of patients or patients with AGC who had a preoperative diagnosis of early gastric cancer. The aim of present study was to compare the short- and long-term outcomes of patients with AGC who underwent LG with those of patients with AGC who underwent OG using a propensity-score matching analysis. METHODS: The study group comprised patients with a preoperative and pathologically confirmed diagnosis of AGC who underwent LG or OG with lymphadenectomy between January 2001 and December 2012 in our hospital. To minimize bias between the LG and OG groups, propensity scores were calculated using a logistic regression model and the following variables: sex, age, body-mass index, American Society of Anesthesiologists physical status class, type of gastrectomy, and clinical and pathological tumor stage. After propensity-score matching, 104 patients (52 who underwent LG and 52 who underwent OG) were studied. RESULTS: LG was associated with significantly earlier initiation of food intake (p <0.01) and a significantly shorter period of postoperative hospitalization (p <0.01). The incidence of all-grade overall, surgical, and medical complications did not differ significantly between the LG group and OG group (p = 0.24, p = 0.12, and p >0.99). Overall and relapse-free survival also did not differ between the LG group and OG group (p = 0.96, p = 0.91). In each tumor stage, overall and relapse-free survival did not differ significantly between the LG group and OG group. CONCLUSION: LG can be a feasible treatment that is beneficial in terms of earlier recovery after operation and can be expected to result in similar survival as OG in patients with AGC.

Cadherin 5 Is a Significant Risk Factor for Hematogenous Recurrence and a Prognostic Factor in Locally Advanced Gastric Cancer.

BACKGROUND/AIM: Cadherin 5 (CDH5) is important for adhesion in epithelial cells, and expressed in tumor cells in several malignancies. In the present study, we evaluated the clinical significance of CDH5 protein expression in locally advanced gastric cancer. MATERIALS AND METHODS: Tumor tissues obtained from 113 patients with advanced gastric adenocarcinoma who underwent gastrectomy were analyzed. RESULTS: High CDH5 expression was significantly associated with recurrence (p=0.017), especially hematological recurrence (p=0.022). High CDH5 expression was a significant risk factor for hematogenous recurrence on multivariate analysis (odds ratio[OR]=3.9, confidential interval [CI] 1.0-15, p=0.043). Patients with high CDH5 expression had a significantly shorter progression-free interval (RFI, p=0.010) than patients with low CDH5 expression. High CDH5 expression was an independent prognostic factor on multivariate analysis of RFI (hazard ratio[HR]=2.2, 95% CI 1.1-4.3, p=0.021). CONCLUSION: CDH5 may play a key role in hematogenous recurrence of advanced gastric cancer and may be a viable treatment target.

High expression of P21-activated kinase 5 protein is associated with poor survival in gastric cancer.

P21-activated kinase 5 (PAK5), also termed PAK7, is one of the six members of the PAK family of serine/threonine kinases, which are downstream effectors in several cancer signaling pathways. PAK5 promotes neural outgrowth, contributes to microtubule stability and induces resistance to apoptosis. However, the clinical importance of PAK5 in gastric cancer has not been comprehensively investigated. In the present study, PAK5 expression was evaluated in gastric cancer tissue samples. Furthermore, the associations between high expression of PAK5, and clinicopathological features and prognosis were examined. PAK5 expression in primary gastric cancer specimens resected from 279 patients who underwent gastrectomy at the Tokyo Medical and Dental University Hospital was evaluated using immunohistochemistry. Of the 279 patients, 44 (15.8%) exhibited high PAK5 expression, which was significantly associated with the differentiated pathological type (differentiated vs. undifferentiated; P<0.001), depth of tumor invasion (T1 vs. T2-T4; P<0.001), lymph node metastasis (N0 vs. N1-N3; P<0.001), presence of distant metastasis or recurrence (present vs. absent; P=0.038), advanced tumor stage (I vs. II-IV; P=0.001) and worse disease-specific survival (P=0.013). In stage I-III disease, 38/254 (15.0%) patients exhibited high PAK5 expression, and high expression of PAK5 was significantly associated with relapse-free interval (P=0.044). PAK5 may serve an important role in tumor progression and influence the outcome of patients with gastric cancer.

High expression of EphA3 (erythropoietin-producing hepatocellular A3) in gastric cancer is associated with metastasis and poor survival.

BACKGROUND: As the major subfamily of receptor tyrosine, erythropoietin-producing hepatocellular (Eph) receptor has been related to progression and prognosis in different types of tumors. However, the role and mechanism of EPHA3 in gastric cancer is still not well understood. METHODS: Specimen were collected from 202 patients who underwent gastric resection for gastric adenocarcinoma. The expression of EphA3 was studied using immunohistochemistry. We analyzed the clinicopathological factors and prognostic relevance of EphA3 expression in gastric cancer. RESULTS: High expression of EphA3 was associated with male predominance (p = 0.031), differentiated histology (p < 0.001), depth of tumor (p = 0.002), lymph node metastasis (p = 0.001), distant metastasis (p = 0.021), liver metastasis (p = 0.024), advanced stage (p < 0.001), and high HER2 expression (p = 0.017). Relapse-free survival (RFS) was significantly worse in patients with high expression of EphA3 than in those with low expression of EphA3 (p = 0.014). Multivariate analysis for RFS showed that depth of tumor [hazard ratio (HR) 9.333, 95% confidence interval (CI) 2.183-39.911, p = 0.003] and lymph node metastasis [hazard ratio (HR) 5.734, 95% confidence interval (CI) 2.349-13.997, p < 0.001] were independent prognostic factors. CONCLUSIONS: These findings suggest that high expression EphA3 may participate in metastasis and worse survival.

Esophagojejunostomy Using the Purse-String Suturing Device After Laparoscopic Total or Proximal Gastrectomy for Gastric Cancer.

BACKGROUND: Performing a safe esophagojejunostomy is important for the standardization of laparoscopic total gastrectomy. We have performed intracorporeal esophagojejunostomy by a circular stapler using the purse-string suturing device that we co-developed. The advantage of this device is that it makes use of the same surgical procedure as open surgery, but it does not depend on the surgeon's technical skills since this device does not require the laparoscopic hand-sewn technique. Furthermore, we have also adapted this device for double-tract reconstruction after laparoscopic proximal gastrectomy. In this study, we present the surgical procedures and postoperative short-term outcomes that were obtained using this novel technique. METHODS: We enrolled 94 patients that underwent intracorporeal esophagojejunostomy by circular stapler using our device after laparoscopic total or proximal gastrectomy for gastric cancer between November 2009 and October 2016. RESULTS: Postoperative complications related to esophagojejunostomy were due to anastomotic stenosis in two cases (2.1%) and leakage of the jejunum stump in one case (1.1%). CONCLUSIONS: Intracorporeal esophagojejunostomy by circular stapler using the purse-string suturing device is safe and feasible. This method can be one of the standard procedures for performing intracorporeal esophagojejunostomy.

Double-tract reconstruction after laparoscopic proximal gastrectomy using detachable ENDO-PSD.

BACKGROUND: Proximal gastrectomy (PG) is widely performed in Japan as a function-preserving surgical approach. Since esophagogastrostomy (EG) was associated with increased reflux symptoms and anastomotic strictures, we have chosen double-tract reconstruction (DTR) as the standard reconstruction method since March 2013. In this study, we described a novel method of laparoscopic DTR using detachable ENDO-PSD and compared its 1-year outcome with EG performed formerly in our institution. METHODS: Patients who underwent laparoscopic PG between May 2005 and July 2014 were retrospectively divided into two groups based on the type of reconstruction and were subsequently analyzed (19 patients in the DTR group and 22 in the EG group). All of them underwent a laparoscopic PG with regional lymph node dissection. In the DTR group, the lower left port site was extended to 4 cm, and an intracorporeal purse-string suture was performed using the detachable ENDO-PSD. The jejunogastrostomy was fashioned on the anterior side of the remnant stomach parallel to the transection line, 2 cm from the cut end. The EG group used the conventional purse-string suture instrument through the 6 cm upper midline mini-laparotomy incision. Patient characteristics, operative data, early operative complications and 1-year postoperative follow-up findings were compared between the two groups. RESULTS: The frequencies of reflux symptoms (10.5 vs. 54.5%, P = 0.003), usage of proton pump inhibitors (31.6 vs. 72.7%, P = 0.008), and anastomotic strictures (0 vs. 27%, P = 0.014) were significantly lower in the DTR group as compared to the EG group. There were no significant differences between the two groups with regard to operation time, blood loss, postoperative hospital stay, postoperative complications, average postoperative/preoperative weight loss ratio, and postoperative/preoperative ratio of biochemical markers (hemoglobin, total protein, albumin, cholesterol). CONCLUSION: Our results indicate that DTR is a useful reconstruction method after PG, especially in terms of preventing reflux esophagitis and anastomotic strictures.

Risk Factor of Pancreatic Fistula after Radical Gastrectomy from the Viewpoint of Fatty Pancreas.

BACKGROUND: We suspected that fatty pancreas, accompanied with metabolic syndrome, may be associated with the incidence of postoperative pancreatic fistula (POPF) after radial gastrectomy. METHODS: Between February 2012 and March 2014, we reviewed consecutive 79 gastric cancer patients who underwent radical gastrectomy. To quantify the degree of fatty infiltration to pancreas by preoperative contrast-enhanced CT, we measured ratios and differences between pancreatic and splenic attenuation values (P/S and P-S, respectively). The optimal cut-off values of P/S and P-S for predicting POPF were determined using the receiver operating characteristic (ROC) curve analysis. Risk factors for POPF of International Study Group on Pancreatic Fistula grade B or higher were examined using univariate and multivariate analyses. RESULTS: POPF occurred in 6 patients (7.6%). ROC curve analyses revealed that the most optimal predictive values of P/S and P-S were 0.74 and -28.8, respectively. Univariate analysis demonstrated that high visceral fat area (p = 0.037), low P/S (p = 0.013), and low P-S (p = 0.006) were significant risk factors of POPF. Multivariate analysis demonstrated that low P/S (OR 10.2 [p = 0.046]) and low P-S (OR 13.2 [p = 0.023]) were significant risk factors of POPF. CONCLUSION: Fatty pancreas is a risk factor of POPF after radical gastrectomy.

TPX2 expression is associated with poor survival in gastric cancer.

BACKGROUND: Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for microtubule formation in human cells. Several studies have demonstrated that TPX2 is overexpressed in multiple tumor types and promotes tumor growth and metastasis. However, there have been few reports regarding its role in gastric cancer. In this study, we evaluated TPX2 expression and investigated its correlations with gastric cancer clinicopathological features and prognosis. METHODS: Tumor samples were obtained from 290 patients with gastric adenocarcinoma who had undergone gastrectomy. The expression of TPX2 protein was examined using immunohistochemical staining. TPX2 messenger RNA (mRNA) levels were evaluated using real-time quantitative reverse transcription PCR in 19 of the gastric cancer tumors and adjacent normal tissues. RESULTS: The mRNA levels of TPX2 were significantly higher in gastric cancer tissues than in matched adjacent normal tissues (p = 0.004). In the immunohistochemical analysis, TPX2 overexpression was found in 123 (42.4%) of 290 patients. High TPX2 expression was positively associated with age, type of histology, depth of tumor, lymph node metastasis, stage, and remote metastasis or recurrence. High TPX2 expression was significantly associated with poorer disease-specific survival (p = 0.004) and relapse-free interval (p = 0.013). CONCLUSIONS: Our results indicated that high TPX2 expression was associated with tumor progression and poor survival in gastric cancer.

Different clinical significance of FGFR1-4 expression between diffuse-type and intestinal-type gastric cancer.

BACKGROUND: Receptor tyrosine kinases promote tumor progression in many cancers, although oncologic activation differs between diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC). Fibroblast growth factor receptor (FGFR) is one RTK, and we previously reported the clinical significance of FGFR1, 2, 3, and 4 in gastric cancer. The aim of the present study was to reevaluate the clinical significance of FGFR1-4 expression separately in DGC and IGC. METHODS: Tumor samples, including 109 DGCs and 100 IGCs, were obtained from patients who underwent gastrectomy between 2003 and 2007 in our institution. The expression levels of FGFR1, 2, 3, and 4 were measured in the tumors by immunohistochemical analysis. RESULTS: In DGC, high expression of FGFR1, FGFR2, or FGFR4 was significantly associated with the depth of invasion, lymph-node metastasis, pathological stage, and distant metastasis or recurrent disease. Patients with high expression of FGFR1, FGFR2, or FGFR4 had significantly poorer disease-specific survival (DSS) (p = 0.009, p = 0.001, and p = 0.023, respectively). In IGC, only FGFR4 expression was significantly associated with factors relative to tumor progression and with shorter DSS (p = 0.012). CONCLUSION: In conclusion, high FGFR4 expression correlated with tumor progression and survival in both DGC and IGC, whereas high expression of FGFR1 and 2 correlated with tumor progression and survival in only DGC.